Fig 1: Validation of gene expression changes in the Hisayama microarray dataset. The association between gene expression and dementia status evaluated in an independently generated AD cohort for four of the DAC and DAC-associated genes identified: AQP4, DTNA, MLC1, and FXYD1. Expression changes measured in three regions: HIP, FCX and TCX. For each gene, plots describe associations with dementia status in each brain region (A–D). In HIP, elevated expression of AQP4 (p = 0.012) and DTNA (p = 0.033) significantly predict dementia status (red, n = 7) compared to healthy individuals (blue, n = 10), while MLC1 (p = 0.075) shows a trend towards elevated expression. In temporal cortex AQP4 (p = 0.02), DTNA (p = 0.031) and FXYD1 (p = 0.017) all significantly predict dementia status (red, n = 10) compared to healthy subjects (blue, n = 19) while MLC1 (p = 0.069) again exhibits a trend towards increased expression. No differences were observed between dementia (red, n = 15) and non-dementia subjects (blue, n = 18). Statistical associations calculated with logistic regression. The bars in (A–D) represent the mean ± the standard error of the mean (S.E.M.). Complete statistical information found in Table 4.
Fig 2: Assessment of the association between protein expression changes and Alzheimer’s disease status. Protein expression and associations with AD status for AQP4, DTNA, MLC1, and FXYD1. Expression changes measured in HIP (ndementia = 10–15, nnon-dementia = 10–12) and FCX (ndementia = 13–20, nnon-dementia = 15–17). For each gene, plots describe associations with AD status in each brain region (A–D). In HIP, elevated expression of DTNA (p = 0.031) and MLC1 (p = 0.025) significantly predict dementia status. Statistical associations calculated with logistic regression. The bars in (A–D) represent the mean ± the standard error of the mean (S.E.M.). Complete statistical information found in Table 4. Representative blots have been cropped for clarity. Dotted lines represent the boundary between cropped images. All blots were processed in parallel across subjects. Full length representative blots can be found in Supplementary Fig. 2.
Fig 3: Novel candidate endfoot gene expression is associated with temporal cortical tau pathology and dementia status. For each gene (A–K, left), expression is quantified for each brain region in cognitively intact subjects (blue, n = 57) and subjects with dementia (red, n = 50). Candidate endfoot gene expression was increased in HIP of subjects with dementia for AMOT (B, t = 2.606, p = 0.014), and MLC1 (G, t = 2.512, p = 0.018). Reduced expression of GLUD1 (F, t = -2.255, p = 0.036) and NDRG2 (H, t = -2.120, p = 0.048) was observed in the TCX among subjects with dementia. All candidate endfoot genes, with exception of NDRG2, PBXIP1 and SLCA1A3 exhibited significant associations with P-tau levels (right). This included ACSS1 (t = 2.573, p = 0.038), AMOT (t = 3.549, p = 0.005), BMPR1B (t = 2.498, p = 0.047), FGFR3 (t = 4.196, p < 0.001), FXYD1 (t = 3.383, p = 0.005), GLUD1 (t = 3.986, p = 0.001), MLC1 (t = 4.115, p < 0.001) and PPAP2B (t = 2.856, p = 0.028). The bars in figures (A–K, left) represent the mean ± the standard deviation (S.D.). The line in figures (A–K, right) represent the least squares (ordinary) fit for all data points that show a significant statistical association. All statistical associations between gene expression and dementia status assessed using logistic regression. All statistical associations between gene expression and pathology indicators were evaluated using OLS regression.
Supplier Page from Abcam for Anti-MLC1 antibody [EPR10942(2)] - N-terminal